Impedance devices for obtaining conductance measurements within luminal organs

ABSTRACT

Impedance devices for obtaining conductance measurements within luminal organs. In at least one embodiment of an impedance device of the present disclosure, the device, comprises an elongated body and an detector positioned upon the elongated body, the detector comprising at least five electrodes and configured to obtain one or more conductance measurements generated using a first arrangement of four of the at least five electrodes and further configured to obtain one or more fluid velocity measurements using a second arrangement of four of the at least five electrodes when the elongated body is positioned within a fluid environment of a mammalian luminal organ, wherein the first arrangement is different from the second arrangement.

PRIORITY

This U.S. patent application is related to, claims the priority benefitof, and is a continuation application of, U.S. patent application Ser.No. 13/282,906, filed Oct. 27, 2011 and issued as U.S. Pat. No.8,886,301 on Nov. 11, 2014, which is related to, claims the prioritybenefit of, and is a continuation-in-part application of, U.S. patentapplication Ser. No. 11/891,981, filed Aug. 14, 2007 and issued as U.S.Pat. No. 8,114,143 on Feb. 14, 2012, which is related to, claims thepriority benefit of, and is a divisional application of, U.S. patentapplication Ser. No. 10/782,149, filed Feb. 19, 2004 and issued as U.S.Pat. No. 7,454,244 on Nov. 18, 2008, which is related to, and claims thepriority benefit of, U.S. Provisional Patent Application Ser. No.60/449,266, filed Feb. 21, 2003, U.S. Provisional Patent ApplicationSer. No. 60/493,145, filed Aug. 7, 2003, and U.S. Provisional PatentApplication Ser. No. 60/502,139, filed Sep. 11, 2003. The contents ofeach of these applications are hereby incorporated by reference in theirentirety into this disclosure.

BACKGROUND

The present disclosure relates generally to medical diagnostics andtreatment equipment, including, but not limited to, devices formeasuring luminal cross-sectional areas of blood vessels, heart valvesand other hollow visceral organs, and methods of using the same.

Coronary Heart Disease

Coronary heart disease is caused by atherosclerotic narrowing of thecoronary arteries. It is likely to produce angina pectoris, heart attackor both. Coronary heart disease caused 466,101 deaths in USA in 1997 andis the single leading cause of death in America today. Approximately, 12million people alive today have a history of heart attack, anginapectoris or both. The break down for males and females is 49% and 51%,respectively. This year, an estimated 1.1 million Americans will have anew or recurrent coronary attack, and more than 40% of the peopleexperiencing these attacks will die as a result. About 225,000 people ayear die of coronary attack without being hospitalized. These are suddendeaths caused by cardiac arrest, usually resulting from ventricularfibrillation. More than 400,000 Americans and 800,000 patientsworld-wide undergo a non-surgical coronary artery interventionalprocedure each year. Although only introduced in the 1990s, in somelaboratories intra-coronary stents are used in 90% of these patients.

Stents increase minimal coronary lumen diameter to a greater degree thanpercutaneous transluminal coronary angioplasty (PTCA) alone according tothe results of two randomized trials using the Palmaz-Schatz stent.These trials compared two initial treatment strategies: stenting aloneand PTCA with “stent backup” if needed. In the STRESS trial, there was asignificant difference in successful angiographic outcome in favor ofstenting (96.1% vs. 89.6%).

Intravascular Ultrasound

Currently intravascular ultrasound is the method of choice to determinethe true diameter of the diseased vessel in order to size the stentcorrectly. The term “vessel,” as used herein, refers generally to anyhollow, tubular, or luminal organ. The tomographic orientation ofultrasound enables visualization of the full 360° circumference of thevessel wall and permits direct measurements of lumen dimensions,including minimal and maximal diameter and cross-sectional area.Information from ultrasound is combined with that obtained byangiography. Because of the latticed characteristics of stents,radiographic contrast material can surround the stent, producing anangiographic appearance of a large lumen, even when the stent struts arenot in full contact with the vessel wall. A large observationalultrasound study after angio-graphically guided stent deploymentrevealed an average residual plaque area of 51% in a comparison ofminimal stent diameter with reference segment diameter, and incompletewall apposition was frequently observed. In this cohort, additionalballoon inflations resulted in a final average residual plaque area of34%, even though the final angiographic percent stenosis was negative(20.7%). These investigators used ultrasound to guide deployment.

However, using intravascular ultrasound as mentioned above requires afirst step of advancement of an ultrasound catheter and then withdrawalof the ultrasound catheter before coronary angioplasty thereby addingadditional time to the stent procedure. Furthermore, it requires anultrasound machine. This adds significant cost and time and more risk tothe procedure.

Aortic Stenosis

Aortic Stenosis (AS) is one of the major reasons for valve replacementsin adult. AS occurs when the aortic valve orifice narrows secondary tovalve degeneration. The aortic valve area is reduced to one fourth ofits normal size before it shows a hemodynamic effect. Because the areaof the normal adult valve orifice is typically 3.0 to 4.0 cm², an area0.75-1.0 cm² is usually not considered severe AS. When stenosis issevere and cardiac output is normal, the mean trans-valvular pressuregradient is generally >50 mmHg. Some patients with severe AS remainasymptomatic, whereas others with only moderate stenosis developsymptoms. Therapeutic decisions, particularly those related tocorrective surgery, are based largely on the presence or absence ofsymptoms.

The natural history of AS in the adult consists of a prolonged latentperiod in which morbidity and mortality are very low. The rate ofprogression of the stenotic lesion has been estimated in a variety ofhemodynamic studies performed largely in patients with moderate AS.Cardiac catheterization and Doppler echocardiographic studies indicatethat some patients exhibit a decrease in valve area of 0.1-0.3 cm² peryear; the average rate of change is 0.12 cm² per year. The systolicpressure gradient across the valve may increase by as much as 10 to 15mmHg per year. However, more than half of the reported patients showedlittle or no progression over a 3-9 year period. Although it appearsthat progression of AS can be more rapid in patients with degenerativecalcific disease than in those with congenital or rheumatic disease, itis not possible to predict the rate of progression in an individualpatient.

Eventually, symptoms of angina, syncope, or heart failure develop aftera long latent period, and the outlook changes dramatically. After onsetof symptoms, average survival is <2-3 years. Thus, the development ofsymptoms identifies a critical point in the natural history of AS.

Many asymptomatic patients with severe AS develop symptoms within a fewyears and require surgery. The incidence of angina, dyspnea, or syncopein asymptomatic patients with Doppler outflow velocities of 4 m/s hasbeen reported to be as high as 38% after 2 years and 79% after 3 years.Therefore, patients with severe AS require careful monitoring fordevelopment of symptoms and progressive disease.

Indications for Cardiac Catheterization

In patients with AS, the indications for cardiac catheterization andangiography are to assess the coronary circulation (to confirm theabsence of coronary artery disease) and to confirm or clarify theclinical diagnosis of AS severity. If echocardiographic data are typicalof severe isolated. AS, coronary angiography may be all that is neededbefore aortic valve replacement (AVR). Complete left- and right-heartcatheterization may be necessary to assess the hemodynamic severity ofAS if there is a discrepancy between clinical and echocardiographic dataor evidence of associated valvular or congenital disease or pulmonaryhypertension.

The pressure gradient across a stenotic valve is related to the valveorifice area and transvalvular flow through Bernoulli's principle. Thus,in the presence of depressed cardiac output, relatively low pressuregradients are frequently obtained in patients with severe AS. On theother hand, during exercise or other high-flow states, systolicgradients can be measured in minimally stenotic valves. For thesereasons, complete assessment of AS requires (1) measurement oftransvalvular flow, (2) determination of the transvalvular pressuregradient, and (3) calculation of the effective valve area. Carefulattention to detail with accurate measurements of pressure and flow isimportant, especially in patients with low cardiac output or a lowtransvalvular pressure gradient.

Problems with Current Aortic Valve Area Measurements

Patients with severe AS and low cardiac output are often present withonly modest transvalvular pressure gradients (i.e., <30 mmHg). Suchpatients can be difficult to distinguish from those with low cardiacoutput and only mild to moderate AS. In both situations, the low-flowstate and low pressure gradient contribute to a calculated effectivevalve area that can meet criteria for severe AS. The standard valve areaformula (simplified Hakki formula which is valve area=cardiacoutput/[pressure gradient]^(1/2)) is less accurate and is known tounderestimate the valve area in low-flow states; under such conditions,it should be interpreted with caution. Although valve resistance is lesssensitive to flow than valve area, resistance calculations have not beenproved to be substantially better than valve area calculations.

In patients with low gradient stenosis and what appears to be moderateto severe AS, it may be useful to determine the transvalvular pressuregradient and calculate valve area and resistance during a baseline stateand again during exercise or pharmacological (i.e., dobutamine infusion)stress. Patients who do not have true, anatomically severe stenosisexhibit an increase in the valve area during an increase in cardiacoutput. In patients with severe AS, these changes may result in acalculated valve area that is higher than the baseline calculation butthat remains in the severe range, whereas in patients without severe AS,the calculated valve area will fall outside the severe range withadministration of dobutamine and indicate that severe AS is not present.

There are many other limitations in estimating aortic valve area inpatients with aortic stenosis using echocardiography and cardiaccatheterization. Accurate measurement of the aortic valve area inpatients with aortic stenosis can be difficult in the setting of lowcardiac output or concomitant aortic or mitral regurgitations.Concomitant aortic regurgitation or low cardiac output can overestimatethe severity of aortic stenosis. Furthermore, because of the dependenceof aortic valve area calculation on cardiac output, any under oroverestimation of cardiac output will cause inaccurate measurement ofvalve area. This is particularly important in patients with tricuspidregurgitation. Falsely measured aortic valve area could causeinappropriate aortic valve surgery in patients who do not need it.

Other Visceral Organs

Visceral organs such as the gastrointestinal tract and the urinary tractserve to transport luminal contents (fluids) from one end of the organto the other end or to an absorption site. The esophagus, for example,transports swallowed material from the pharynx to the stomach. Diseasesmay affect the transport function of the organs by changing the luminalcross-sectional area, the peristalsis generated by muscle, or bychanging the tissue components. For example, strictures in the esophagusand urethra constitute a narrowing of the organ where fibrosis of thewall may occur. Strictures and narrowing can be treated with distension,much like the treatment of plaques in the coronary arteries.

BRIEF SUMMARY

The present disclosure provides for various devices and systems formeasuring cross-sectional areas and pressure gradients in luminalorgans. The present disclosure also comprises a method and apparatus formeasuring cross-sectional areas and pressure gradients in luminalorgans, such as, for example, blood vessels, heart valves, and othervisceral hollow organs.

In at least one embodiment, an exemplary system of the presentdisclosure comprises an impedance catheter capable of being introducedinto a treatment site, a solution delivery source for injecting asolution through the catheter into the treatment site, a constantcurrent source enabling the supply of constant electrical current to thetreatment site, and a data acquisition system enabling the measurementof parallel conductance at the treatment site, whereby enablingcalculation of cross-sectional area at the treatment site.

In at least one embodiment of an impedance device of the presentdisclosure, the device, comprises an elongated body and an detectorpositioned upon the elongated body, the detector comprising at leastfive electrodes and configured to obtain one or more conductancemeasurements generated using a first arrangement of four of the at leastfive electrodes and further configured to obtain one or more fluidvelocity measurements using a second arrangement of four of the at leastfive electrodes when the elongated body is positioned within a fluidenvironment of a mammalian luminal organ, wherein the first arrangementis different from the second arrangement. In another embodiment, theelongated body is selected from the group consisting of a wire and acatheter. In yet another embodiment, at least three electrodes of the atleast five electrodes are capable of excitation to generate an electricfield when a current source capable of supplying electrical current tothe at least three electrodes is operably coupled thereto, and at leasttwo electrodes of the at least five electrodes are capable of arecapable of obtaining one or more luminal organ measurements selectedfrom the group consisting of the one or more conductance measurementsand the one or more fluid velocity measurements. In an additionalembodiment, when the at least two electrodes are operably connected to adata acquisition and processing system, the data acquisition andprocessing system is capable of receiving the one or more luminal organmeasurements and calculating a cross-sectional area of the luminal organbased in part upon the one or more luminal organ measurements and aknown distance between the at least two electrodes.

In at least one embodiment of an impedance device of the presentdisclosure, the at least five electrodes comprise five electrodescomprising a most distal electrode, an electrode immediately adjacent tothe most distal electrode, a most proximal electrode, an electrodeimmediately adjacent to the most proximal electrode, and a centralelectrode positioned between the electrode immediately adjacent to themost distal electrode and the electrode immediately adjacent to the mostproximal electrode. In an additional embodiment, the first arrangementof electrodes comprises the most distal electrode, the electrodeimmediately adjacent to the most distal electrode, the centralelectrode, and the electrode immediately adjacent to the most proximalelectrode, wherein the most distal electrode and the electrodeimmediately adjacent to the most proximal electrode are capable ofexcitation to generate an electric field, and wherein the electrodeimmediately adjacent to the most distal electrode and the centralelectrode are configured to obtain the one or more conductancemeasurements within the electric field. In yet an additional embodiment,when the elongated body is positioned within a fluid environment of amammalian luminal organ and when the fluid environment includes anindicator, the most proximal electrode is operable to detect theindicator, and detection of the indicator facilitates activation of thefirst arrangement of electrodes so that the first arrangement ofelectrodes can obtain the one or more conductance measurements withinthe electric field. In another embodiment, one or more cross-sectionalareas can be calculated based in part upon the one or more conductancemeasurements and a known distance between the electrode immediatelyadjacent to the most distal electrode and the central electrode.

In at least one embodiment of an impedance device of the presentdisclosure, the second arrangement of electrodes comprises the mostdistal electrode, the electrode immediately adjacent to the most distalelectrode, the central electrode, and the most proximal electrode,wherein the most distal electrode and the most proximal electrode arecapable of excitation to generate an electric field, wherein the mostdistal electrode and the electrode immediately adjacent to the mostdistal electrode comprise a first fluid velocity detection electrodepair, and wherein the central electrode and the most proximal electrodecomprise a second fluid velocity detection pair. In another embodiment,when the elongated body is positioned within the fluid environment andthe fluid environment comprises an indicator, movement of the indicatorpast the first fluid velocity detection electrode pair and the secondfluid velocity detection electrode pair allows the first fluid velocitydetection electrode pair and the second fluid velocity detectionelectrode pair to obtain the one or more fluid velocity measurements. Inyet another embodiment, the most distal electrode is spaced at or about4 mm from the an electrode immediately adjacent to the most distalelectrode, the electrode immediately adjacent to the most distalelectrode is spaced at or about 1 mm from the central electrode, thecentral electrode is spaced at or about 4 mm from the electrodeimmediately adjacent to the most proximal electrode, and the electrodeimmediately adjacent to the most proximal electrode is spaced at orabout 8 mm from the most proximal electrode. In an additionalembodiment, the most distal electrode is spaced at or about 3 mm fromthe an electrode immediately adjacent to the most distal electrode, theelectrode immediately adjacent to the most distal electrode is spaced ator about 3 mm from the central electrode, and the central electrode isspaced at or about 6 mm from the electrode immediately adjacent to themost proximal electrode.

In at least one embodiment of an impedance device of the presentdisclosure, the at least five electrodes comprise eight electrodescomprising a most distal electrode, an electrode immediately adjacent tothe most distal electrode, a most proximal electrode, an electrodeimmediately adjacent to the most proximal electrode, a central distalelectrode, a central proximal electrode, an electrode immediatelyadjacent to and distal to the central distal electrode, and an electrodeimmediately adjacent to and proximal to the central proximal electrode.

In an additional embodiment, the most distal electrode and the centraldistal electrode are capable of excitation to generate a distal electricfield, the electrode immediately adjacent to and distal to the centraldistal electrode and the electrode immediately adjacent to and proximalto the central proximal electrode are capable of excitation to generatea central electric field, the central proximal electrode and the mostproximal electrode are capable of excitation to generate a proximalelectric field, the one or more conductance measurements can be obtainedwithin each of the distal electric field, the central electric field,and the proximal electric field, and one or more cross-sectional areascan be calculated based in part upon the one or more conductancemeasurements and known distances between the electrodes used to generatethe distal electric field, the central electric field, and the proximalelectric field. In yet an additional embodiment, the second arrangementof electrodes comprises the most distal electrode, the central distalelectrode, the central proximal electrode, and the most proximalelectrode, wherein the most distal electrode and the central distalelectrode comprise a first fluid velocity detection electrode pair, andwherein the central proximal electrode and the most proximal electrodecomprise a second fluid velocity detection pair. In another embodiment,when the elongated body is positioned within the fluid environment andthe fluid environment comprises an indicator, movement of the indicatorpast the first fluid velocity detection electrode pair and the secondfluid velocity detection electrode pair allows the first fluid velocitydetection electrode pair and the second fluid velocity detectionelectrode pair to obtain the one or more fluid velocity measurements.

In at least one embodiment of an impedance device of the presentdisclosure, the most distal electrode is spaced at or about 3 mm fromthe electrode immediately adjacent to the most distal electrode, theelectrode immediately adjacent to the most distal electrode is spaced ator about 2 mm from the electrode immediately adjacent to and distal tothe central distal electrode, the electrode immediately adjacent to anddistal to the central distal electrode is spaced at or about 6 mm fromthe central distal electrode, the central distal electrode is spaced ator about 2 mm from the central proximal electrode, the central proximalelectrode is spaced at or about 6 mm from the electrode immediatelyadjacent to and proximal to the central proximal electrode, theelectrode immediately adjacent to and proximal to the central proximalelectrode is spaced at or about 2 mm from the electrode immediatelyadjacent to the most proximal electrode, and the electrode immediatelyadjacent to the most proximal electrode is spaced at or about 3 mm fromthe most proximal electrode. In another embodiment, the device furthercomprises an inflatable balloon positioned along the longitudinal axisof the elongated body located proximal to the detector, wherein theinflatable balloon is in communication with a lumen defined within theelongated body. In yet another embodiment, the device further comprisesa tetrapolar detector positioned upon the elongated body within theballoon, the tetrapolar detector comprising two excitation electrodesand two detection electrodes operable to obtain one or more ballooncross-sectional areas.

In at least one embodiment of an impedance device of the presentdisclosure, the device comprises an elongated body and an detectorpositioned upon the elongated body, the detector comprising fourelectrodes configured to obtain one or more conductance measurementswithin a luminal organ of at least about 4 mm in diameter, the fourelectrodes comprising a most distal electrode, an electrode immediatelyadjacent to the most distal electrode, a most proximal electrode, and anelectrode immediately adjacent to the most proximal electrode, whereinthe most distal electrode is spaced at or about 3 mm from the anelectrode immediately adjacent to the most distal electrode, wherein theelectrode immediately adjacent to the most distal electrode is spaced ator about 3 mm from the electrode immediately adjacent to the mostproximal electrode, and wherein the electrode immediately adjacent tothe most proximal electrode is spaced at or about 6 mm from the mostproximal electrode.

In at least one embodiment of a method for using an impedance device toobtain a luminal cross-sectional area measurement and a fluid velocitymeasurement of the present disclosure, the method comprises the steps ofintroducing at least part of an impedance device into a luminal organ ata first location, the impedance device comprising an elongated body anda detector positioned upon the elongated body, the detector comprising amost distal electrode, an electrode immediately adjacent to the mostdistal electrode, a most proximal electrode, an electrode immediatelyadjacent to the most proximal electrode, and a central electrodepositioned between the electrode immediately adjacent to the most distalelectrode and the electrode immediately adjacent to the most proximalelectrode, applying current to the impedance device using a currentsource, and obtaining, in either order, (a) one or more conductancemeasurements by exciting the most distal electrode and the electrodeimmediately adjacent to the most proximal electrode to generate anelectric field and detecting using the electrode immediately adjacent tothe most distal electrode and the central electrode within the electricfield, wherein one or more cross-sectional areas can be calculated basedin part upon the one or more conductance measurements and a knowndistance between the electrode immediately adjacent to the most distalelectrode and the central electrode, and (b) one or more fluid velocitymeasurements by exciting the most distal electrode and the most proximalelectrode are capable of excitation to generate an electric field,wherein the most distal electrode and the electrode immediately adjacentto the most distal electrode comprise a first fluid velocity detectionelectrode pair, wherein the central electrode and the most proximalelectrode comprise a second fluid velocity detection pair, and whereinthe first fluid velocity detection electrode pair and the second fluidvelocity detection electrode pair are operable obtain the one or morefluid velocity measurements by detecting an indicator positioned withinthe luminal organ. In another embodiment, the method further comprisesthe step of implanting a stent within the luminal organ using aninflatable balloon coupled to the impedance device, wherein the stent ispositioned upon the inflatable balloon prior to implantation within theluminal organ.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A shows a balloon catheter having impedance measuring electrodessupported in front of the stenting balloon, according to an embodimentof the present disclosure;

FIG. 1B shows a balloon catheter having impedance measuring electrodeswithin and in front of the balloon, according to an embodiment of thepresent disclosure;

FIG. 1C shows a catheter having an ultrasound transducer within and infront of balloon, according to an embodiment of the present disclosure;

FIG. 1D shows a catheter without a stenting balloon, according to anembodiment of the present disclosure;

FIG. 1E shows a guide catheter with wire and impedance electrodes,according to an embodiment of the present disclosure;

FIG. 1F shows a catheter with multiple detection electrodes, accordingto an embodiment of the present disclosure;

FIG. 2A shows a catheter in cross-section proximal to the location ofthe sensors showing the leads embedded in the material of the probe,according to an embodiment of the present disclosure;

FIG. 2B shows a catheter in cross-section proximal to the location ofthe sensors showing the leads run in separate lumens, according to anembodiment of the present disclosure;

FIG. 3 is a schematic of one embodiment of the system showing a cathetercarrying impedance measuring electrodes connected to the dataacquisition equipment and excitation unit for the cross-sectional areameasurement, according to an embodiment of the present disclosure;

FIG. 4A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 1.5% NaCl solution, accordingto an embodiment of the present disclosure;

FIG. 4B shows the peak-to-peak envelope of the detected voltage shown inFIG. 4A, according to an embodiment of the present disclosure;

FIG. 5A shows the detected filtered voltage drop as measured in theblood stream before and after injection of 0.5% NaCl solution, accordingto an embodiment of the present disclosure;

FIG. 5B shows the peak-to-peak envelope of the detected voltage shown inFIG. 5A, according to an embodiment of the present disclosure;

FIG. 6 shows balloon distension of the lumen of the coronary artery,according to an embodiment of the present disclosure;

FIG. 7A shows balloon distension of a stent into the lumen of thecoronary artery, according to an embodiment of the present disclosure;

FIG. 7B shows the voltage recorded by a conductance catheter with aradius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 0.5%NaCl bolus is injected into the treatment site, according to anembodiment of the present disclosure;

FIG. 7C shows the voltage recorded by a conductance catheter with aradius of 0.55 mm for various size vessels (vessel radii of 3.1, 2.7,2.3, 1.9, 1.5 and 0.55 mm for the six curves, respectively) when a 1.5%NaCl bolus is injected into the treatment site, according to anembodiment of the present disclosure;

FIG. 8A shows an exemplary device operable to obtain one or more sizingmeasurements and one or more fluid velocity measurements, according toan embodiment of the present disclosure;

FIG. 8B shows an exemplary device with a balloon coupled thereto, thedevice operable to obtain one or more sizing measurements and one ormore fluid velocity measurements, according to an embodiment of thepresent disclosure; and

FIGS. 9A-10B show exemplary devices having various numbers of electrodesand various spacings therebetween, according to exemplary embodiments ofthe present disclosure.

DETAILED DESCRIPTION

For the purposes of promoting an understanding of the principles of thepresent disclosure, reference will now be made to the embodimentsillustrated in the drawings, and specific language will be used todescribe the same. It will nevertheless be understood that no limitationof the scope of this disclosure is thereby intended.

This present disclosure makes accurate measures of the luminalcross-sectional area of organ stenosis within acceptable limits toenable accurate and scientific stent sizing and placement in order toimprove clinical outcomes by avoiding under or over deployment and underor over sizing of a stent which can cause acute closure or in-stentre-stenosis. In one embodiment, an angioplasty or stent balloon includesimpedance electrodes supported by the catheter in front of the balloon.These electrodes enable the immediate measurement of the cross-sectionalarea of the vessel during the balloon advancement. This provides adirect measurement of non-stenosed area and allows the selection of theappropriate stent size. In one approach, error due to the loss ofcurrent in the wall of the organ and surrounding tissue is corrected byinjection of two solutions of NaCl or other solutions with knownconductivities. In another embodiment impedance electrodes are locatedin the center of the balloon in order to deploy the stent to the desiredcross-sectional area. These embodiments and procedures substantiallyimprove the accuracy of stenting and the outcome and reduce the cost.

Other embodiments make diagnosis of valve stenosis more accurate andmore scientific by providing a direct accurate measurement ofcross-sectional area of the valve annulus, independent of the flowconditions through the valve. Other embodiments improve evaluation ofcross-sectional area and flow in organs like the gastrointestinal tractand the urinary tract.

Embodiments of the present disclosure overcome the problems associatedwith determination of the size (cross-sectional area) of luminal organs,such as, for example, in the coronary arteries, carotid, femoral, renaland iliac arteries, aorta, gastrointestinal tract, urethra and ureter.Embodiments also provide methods for registration of acute changes inwall conductance, such as, for example, due to edema or acute damage tothe tissue, and for detection of muscle spasms/contractions.

As described below, in one preferred embodiment, there is provided anangioplasty catheter with impedance electrodes near the distal end 19 ofthe catheter (i.e., in front of the balloon) for immediate measurementof the cross-sectional area of a vessel lumen during balloonadvancement. This catheter includes electrodes for accurate detection oforgan luminal cross-sectional area and ports for pressure gradientmeasurements. Hence, it is not necessary to change catheters such aswith the current use of intravascular ultrasound. In one preferredembodiment, the catheter provides direct measurement of the non-stenosedarea, thereby allowing the selection of an appropriately sized stent. Inanother embodiment, additional impedance electrodes may be incorporatedin the center of the balloon on the catheter in order to deploy thestent to the desired cross-sectional area. The procedures describedherein substantially improve the accuracy of stenting and improve thecost and outcome as well.

In another embodiment, the impedance electrodes are embedded within acatheter to measure the valve area directly and independent of cardiacoutput or pressure drop and therefore minimize errors in the measurementof valve area. Hence, measurements of area are direct and not based oncalculations with underlying assumptions. In another embodiment,pressure sensors can be mounted proximal and distal to the impedanceelectrodes to provide simultaneous pressure gradient recording.

Device and System Embodiments

We designed and build the impedance or conductance catheters illustratedin FIGS. 1A-1F. With reference to the exemplary embodiment shown in FIG.1A, four wires were threaded through one of the 2 lumens of a 4 Frcatheter. Here, electrodes 26 and 28, are spaced 1 mm apart and form theinner (detection) electrodes. Electrodes 25 and 27 are spaced 4-5 mmfrom either side of the inner electrodes and form the outer (excitation)electrodes.

In one approach, dimensions of a catheter to be used for any givenapplication depend on the optimization of the potential field usingfinite element analysis described below. For small organs or inpediatric patients the diameter of the catheter may be as small as 0.3mm. In large organs the diameter may be significantly larger dependingon the results of the optimization based on finite element analysis. Theballoon size will typically be sized according to the preferreddimension of the organ after the distension. The balloon may be made ofmaterials, such as, for example, polyethylene, latex,polyestherurethane, or combinations thereof. The thickness of theballoon will typically be on the order of a few microns. The catheterwill typically be made of PVC or polyethylene, though other materialsmay equally well be used. The excitation and detection electrodestypically surround the catheter as ring electrodes but they may also bepoint electrodes or have other suitable configurations. These electrodesmay be made of any conductive material, preferably of platinum iridiumor a carbon-coasted surface to avoid fibrin deposits. In the preferredembodiment, the detection electrodes are spaced with 0.5-1 mm betweenthem and with a distance between 4-7 mm to the excitation electrodes onsmall catheters. The dimensions of the catheter selected for a treatmentdepend on the size of the vessel and are preferably determined in parton the results of finite element analysis, described below. On largecatheters, for use in larger vessels and other visceral hollow organs,the electrode distances may be larger.

Referring to FIGS. 1A, 1B, 1C and 1D, several embodiments of thecatheters are illustrated. The catheters shown contain to a varyingdegree different electrodes, number and optional balloon(s). Withreference to the embodiment shown in FIG. 1A, there is shown animpedance catheter 20 with 4 electrodes 25, 26, 27 and 28 placed closeto the tip 19 of the catheter. Proximal to these electrodes is anangiography or stenting balloon 30 capable of being used for treatingstenosis. Electrodes 25 and 27 are excitation electrodes, whileelectrodes 26 and 28 are detection electrodes, which allow measurementof cross-sectional area during advancement of the catheter, as describedin further detail below. The portion of the catheter 20 within balloon30 includes an infusion port 35 and a pressure port 36.

The catheter 20 may also advantageously include several miniaturepressure transducers (not shown) carried by the catheter or pressureports for determining the pressure gradient proximal at the site wherethe cross-sectional area is measured. The pressure is preferablymeasured inside the balloon and proximal, distal to and at the locationof the cross-sectional area measurement, and locations proximal anddistal thereto, thereby enabling the measurement of pressure recordingsat the site of stenosis and also the measurement of pressure-differencealong or near the stenosis. In one embodiment, shown in FIG. 1A,Catheter 20 advantageously includes pressure port 90 and pressure port91 proximal to or at the site of the cross-sectional measurement forevaluation of pressure gradients. As described below with reference toFIGS. 2A, 2B and 3, in one embodiment, the pressure ports are connectedby respective conduits in the catheter 20 to pressure sensors in thedata acquisition system 100. Such pressure sensors are well known in theart and include, for example, fiber-optic systems, miniature straingauges, and perfused low-compliance manometry.

In one embodiment, a fluid-filled silastic pressure-monitoring catheteris connected to a pressure transducer. Luminal pressure can be monitoredby a low compliance external pressure transducer coupled to the infusionchannel of the catheter. Pressure transducer calibration was carried outby applying 0 and 100 mmHg of pressure by means of a hydrostatic column.

In one embodiment, shown in FIG. 1B, the catheter 39 includes anotherset of excitation electrodes 40, 41 and detection electrodes 42, 43located inside the angioplastic or stenting balloon 30 for accuratedetermination of the balloon cross-sectional area during angioplasty orstent deployment. These electrodes are in addition to electrodes 25, 26,27 and 28.

In one embodiment, the cross-sectional area may be measured using atwo-electrode system. In another embodiment, illustrated in FIG. 1F,several cross-sectional areas can be measured using an array of 5 ormore electrodes. Here, the excitation electrodes 51, 52, are used togenerate the current while detection electrodes 53, 54, 55, 56 and 57are used to detect the current at their respective sites.

The tip of the catheter can be straight, curved or with an angle tofacilitate insertion into the coronary arteries or other lumens, suchas, for example, the biliary tract. The distance between the balloon andthe electrodes is usually small, in the 0.5-2 cm range but can be closeror further away, depending on the particular application or treatmentinvolved.

In another embodiment, shown in FIG. 1C the catheter 21 has one or moreimaging or recording device, such as, for example, ultrasoundtransducers 50 for cross-sectional area and wall thickness measurements.As shown in this embodiment, the transducers 50 are located near thedistal tip 19 of the catheter 21.

FIG. 1D shows an embodiment of the impedance catheter 22 without anangioplastic or stenting balloon. This catheter also possesses aninfusion or injection port 35 located proximal relative to theexcitation electrode 25 and pressure port 36.

With reference to the embodiment shown in FIG. 1E, the electrodes 25,26, 27, 28 can also be built onto a wire 18, such as, for example, apressure wire, and inserted through a guide catheter 23 where theinfusion of bolus can be made through the lumen of the guide catheter37.

With reference to the embodiments shown in FIGS. 1A, 1B, 1C, 1D, 1E and1F, the impedance catheter advantageously includes optional ports 35,36, 37 for suction of contents of the organ or infusion of fluid. Thesuction/infusion port 35, 36, 37 can be placed as shown with the balloonor elsewhere both proximal or distal to the balloon on the catheter. Thefluid inside the balloon can be any biologically compatible conductingfluid. The fluid to inject through the infusion port or ports can be anybiologically compatible fluid but the conductivity of the fluid isselected to be different from that of blood (e.g., NaCl).

In another embodiment (not illustrated), the catheter contains an extrachannel for insertion of a guide wire to stiffen the flexible catheterduring the insertion or data recording. In yet another embodiment (notillustrated), the catheter includes a sensor for measurement of the flowof fluid in the body organ.

System for Determining Cross-Sectional Area and Pressure Gradient

The Operation of the Impedance Catheter 20 is as Follows:

With reference to the embodiment shown in FIG. 1A for electrodes 25, 26,27, 28, conductance of current flow through the organ lumen and organwall and surrounding tissue is parallel; i.e.,

$\begin{matrix}{{G\left( {z,t} \right)} = {\frac{{{CSA}\left( {z,t} \right)} \cdot C_{b}}{L\;} + {G_{p}\left( {z,t} \right)}}} & \left\lbrack {1a} \right\rbrack\end{matrix}$

where G_(p)(z,t) is the effective conductance of the structure outsidethe bodily fluid (organ wall and surrounding tissue), and C_(b) is thespecific electrical conductivity of the bodily fluid which for bloodgenerally depends on the temperature, hematocrit and orientation anddeformation of blood cells and L is the distance between the detectionelectrodes. Equation [1] can be rearranged to solve for cross sectionalarea CSA(t), with a correction factor, α, if the electric field isnon-homogeneous, as

$\begin{matrix}{{{CSA}\left( {z,t} \right)} = {\frac{L}{\alpha \; C_{b}}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \left\lbrack {1b} \right\rbrack\end{matrix}$

where α would be equal to 1 if the field were completely homogeneous.The parallel conductance, G_(p), is an offset error that results fromcurrent leakage. G_(p) would equal 0 if all of the current were confinedto the blood and hence would correspond to the cylindrical model givenby Equation [10]. In one approach, finite element analysis is used toproperly design the spacing between detection and excitation electrodesrelative to the dimensions of the vessel to provide a nearly homogenousfield such that a can be considered equal to 1. Our simulations showthat a homogenous or substantially homogenous field is provided by (1)the placement of detection electrodes substantially equidistant from theexcitation electrodes and (2) maintaining the distance between thedetection and excitation electrodes substantially comparable to thevessel diameter. In one approach, a homogeneous field is achieved bytaking steps (1) and/or (2) described above so that α is equals 1 in theforegoing analysis.

At any given position, z, along the long axis of organ and at any giventime, t, in the cardiac cycle, G_(p) is a constant. Hence, twoinjections of different concentrations and/or conductivities of NaClsolution give rise to two Equations:

C ₁·CSA(z,t)+L·G _(p)(z,t)=L·G ₁(z,t)  [2]

and

C ₂·CSA(z,t)+L·G _(p)(z,t)=L·G ₂(z,t)  [3]

which can be solved simultaneously for CSA and G_(p) as

$\begin{matrix}{{{{CSA}\left( {z,t} \right)} = {L\frac{\left\lbrack {{G_{2}\left( {z,t} \right)} - {G_{1}\left( {z,t} \right)}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}}}{and}} & \lbrack 4\rbrack \\{{G_{p}\left( {z,t} \right)} = \frac{\left\lbrack {{C_{2} \cdot {G_{1}\left( {z,t} \right)}} - {C_{1} \cdot {G_{2}\left( {z,t} \right)}}} \right\rbrack}{\left\lbrack {C_{2} - C_{1}} \right\rbrack}} & \lbrack 5\rbrack\end{matrix}$

where subscript “1” and subscript “2” designate any two injections ofdifferent NaCl concentrations and/or conductivities. For each injectionk, C_(k) gives rise to G_(k) which is measured as the ratio of the rootmean square of the current divided by the root mean square of thevoltage. The C_(k) is typically determined through in vitro calibrationfor the various NaCl concentrations and/or conductivities. Theconcentration of NaCl used is typically on the order of 0.45 to 1.8%.The volume of NaCl solution is typically about 5 ml, but sufficient todisplace the entire local vascular blood volume momentarily. The valuesof CSA(t) and G_(p)(t) can be determined at end-diastole or end-systole(i.e., the minimum and maximum values) or the mean thereof.

Once the CSA and G_(p) of the vessel are determined according to theabove embodiment, rearrangement of Equation [1] allows the calculationof the specific electrical conductivity of blood in the presence ofblood flow as

$\begin{matrix}{C_{b} = {\frac{L}{{CSA}\left( {z,t} \right)}\left\lbrack {{G\left( {z,t} \right)} - {G_{p}\left( {z,t} \right)}} \right\rbrack}} & \lbrack 6\rbrack\end{matrix}$

In this way, Equation [1b] can be used to calculate the CSA continuously(temporal variation as for example through the cardiac cycle) in thepresence of blood.

In one approach, a pull or push through is used to reconstruct thevessel along its length. During a long injection (e.g., 10-15 s), thecatheter can be pulled back or pushed forward at constant velocity U.Equation [1b] can be expressed as

$\begin{matrix}{{{CSA}\left( {{U \cdot t},t} \right)} = {\frac{L}{C_{b}}\left\lbrack {{G\left( {{U \cdot t},t} \right)} - {G_{p}\left( {U \cdot \left( {t,t} \right)} \right\rbrack}} \right.}} & \lbrack 7\rbrack\end{matrix}$

where the axial position, z, is the product of catheter velocity, U, andtime, t; i.e., z=U·t.

For the two injections, denoted by subscript “1” and subscript “2”,respectively, we can consider different time points T1, T2, etc. suchthat Equation [7] can be written as

$\begin{matrix}{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}} & \left\lbrack {8a} \right\rbrack \\{{{{CSA}_{1}\left( {{U \cdot T_{1}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{1}},t} \right)} - {G_{p\; 1}\left( {{U \cdot T_{1}},t} \right)}} \right\rbrack}}{and}} & \left\lbrack {8b} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{1}}\left\lbrack {{G_{1}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {9a} \right\rbrack \\{{{CSA}_{2}\left( {{U \cdot T_{2}},t} \right)} = {\frac{L}{C_{2}}\left\lbrack {{G_{2}\left( {{U \cdot T_{2}},t} \right)} - {G_{p\; 2}\left( {{U \cdot T_{2}},t} \right)}} \right\rbrack}} & \left\lbrack {9b} \right\rbrack\end{matrix}$

and so on. Each set of Equations [8a], [8b] and [9a], [9b], etc. can besolved for CSA₁, G_(p1) and CSA₂, G_(p2), respectively. Hence, we canmeasure the CSA at various time intervals and hence of differentpositions along the vessel to reconstruct the length of the vessel. Inone embodiment, the data on the CSA and parallel conductance as afunction of longitudinal position along the vessel can be exported froman electronic spreadsheet, such as, for example, an Excel file, toAutoCAD where the software uses the coordinates to render a3-Dimensional vessel on the monitor.

For example, in one exemplary approach, the pull back reconstruction wasmade during a long injection where the catheter was pulled back atconstant rate by hand. The catheter was marked along its length suchthat the pull back was made at 2 mm/sec. Hence, during a 10 secondinjection, the catheter was pulled back about 2 cm. The data wascontinuously measured and analyzed at every two second interval; i.e.,at every 4 mm. Hence, six different measurements of CSA and G_(p) weremade which were used to reconstruction the CSA and G_(p) along thelength of the 2 cm segment.

Operation of the Impedance Catheter 39:

With reference to the embodiment shown in FIG. 1B, the voltagedifference between the detection electrodes 42 and 43 depends on themagnitude of the current (I) multiplied by the distance (D) between thedetection electrodes and divided by the conductivity (C) of the fluidand the cross-sectional area (CSA) of the artery or other organs intowhich the catheter is introduced. Since the current (I), the distance(L) and the conductivity (C) normally can be regarded as calibrationconstants, an inverse relationship exists between the voltage differenceand the CSA as shown by the following Equations:

$\begin{matrix}{{{\Delta \; V} = \frac{I \cdot L}{C \cdot {CSA}}}{or}} & \left\lbrack {10a} \right\rbrack \\{{CSA} = \frac{G \cdot L}{C}} & \left\lbrack {10b} \right\rbrack\end{matrix}$

where G is conductance expressed as the ratio of current to voltage(I/ΔV). Equation [10] is identical to Equation [1b] if we neglect theparallel conductance through the vessel wall and surrounding tissuebecause the balloon material acts as an insulator. This is thecylindrical model on which the conductance method is used.

As described below with reference to FIGS. 2A, 2B, 3, 4 and 5, theexcitation and detection electrodes are electrically connected toelectrically conductive leads in the catheter for connecting theelectrodes to the data acquisition system 100.

FIGS. 2A and 2B illustrate two embodiments 20A and 20B of the catheterin cross-section. Each embodiment has a lumen 60 for inflating anddeflating the balloon and a lumen 61 for suction and infusion. The sizesof these lumens can vary in size. The impedance electrode electricalleads 70A are embedded in the material of the catheter in the embodimentin FIG. 2A, whereas the electrode electrical leads 70B are tunneledthrough a lumen 71 formed within the body of catheter 70B in FIG. 2B.

Pressure conduits for perfusion manometry connect the pressure ports 90,91 to transducers included in the data acquisition system 100. As shownin FIG. 2A pressure conduits 95A may be formed in 20A. In anotherembodiment, shown in FIG. 2B, pressure conduits 95B constituteindividual conduits within a tunnel 96 formed in catheter 20B. In theembodiment described above where miniature pressure transducers arecarried by the catheter, electrical conductors will be substituted forthese pressure conduits.

With reference to FIG. 3, in one embodiment, the catheter 20 connects toa data acquisition system 100, to a manual or automatic system 105 fordistension of the balloon and to a system 106 for infusion of fluid orsuction of blood. The fluid will be heated to 37-39° or equivalent tobody temperature with heating unit 107. The impedance planimetry systemtypically includes a current unit, amplifiers and signal conditioners.The pressure system typically includes amplifiers and signalconditioners. The system can optionally contain signal conditioningequipment for recording of fluid flow in the organ.

In one preferred embodiment, the system is pre-calibrated and the probeis available in a package. Here, the package also preferably containssterile syringes with the fluids to be injected. The syringes areattached to the machine and after heating of the fluid by the machineand placement of the probe in the organ of interest, the user presses abutton that initiates the injection with subsequent computation of thedesired parameters. The CSA and parallel conductance and other relevantmeasures such as distensibility, tension, etc. will typically appear onthe display panel in the PC module 160. Here, the user can then removethe stenosis by distension or by placement of a stent.

If more than one CSA is measured, the system can contain a multiplexerunit or a switch between CSA channels. In one embodiment, each CSAmeasurement will be through separate amplifier units. The same mayaccount for the pressure channels.

In one embodiment, the impedance and pressure data are analog signalswhich are converted by analog-to-digital converters 150 and transmittedto a computer 160 for on-line display, on-line analysis and storage. Inanother embodiment, all data handling is done on an entirely analogbasis. The analysis advantageously includes software programs forreducing the error due to conductance of current in the organ wall andsurrounding tissue and for displaying the 2D or 3D-geometry of the CSAdistribution along the length of the vessel along with the pressuregradient. In one embodiment of the software, a finite element approachor a finite difference approach is used to derive the CSA of the organstenosis taking parameters such as conductivities of the fluid in theorgan and of the organ wall and surrounding tissue into consideration.In another embodiment, simpler circuits are used; e.g., based on makingtwo or more injections of different NaCl solutions to vary theresistivity of fluid in the vessel and solving the two simultaneousEquations [2] and [3] for the CSA and parallel conductance (Equations[4] and [5], respectively). In another embodiment, the software containsthe code for reducing the error in luminal CSA measurement by analyzingsignals during interventions such as infusion of a fluid into the organor by changing the amplitude or frequency of the current from thecurrent amplifier, which may be a constant current amplifier. Thesoftware chosen for a particular application, preferably allowscomputation of the CSA with only a small error instantly or withinacceptable time during the medical procedure.

In one approach, the wall thickness is determined from the parallelconductance for those organs that are surrounded by air ornon-conducting tissue. In such cases, the parallel conductance is equalto

$\begin{matrix}{G_{p} = \frac{{CSA}_{w} \cdot C_{w}}{L}} & \left\lbrack {11a} \right\rbrack\end{matrix}$

where CSA_(w) is the wall area of the organ and C_(w) is the electricalconductivity through the wall. This Equation can be solved for the wallCSA_(w) as

$\begin{matrix}{{CSA}_{w} = \frac{G_{p} \cdot L}{C_{w}}} & \left\lbrack {11b} \right\rbrack\end{matrix}$

For a cylindrical organ, the wall thickness, h, can be expressed as

$\begin{matrix}{h = \frac{{CSA}_{w}}{\pi \; D}} & \lbrack 12\rbrack\end{matrix}$

where D is the diameter of the vessel which can be determined from thecircular CSA (D=[4CSA/π]^(1/2)).

When the CSA, pressure, wall thickness, and flow data are determinedaccording to the embodiments outlined above, it is possible to computethe compliance (e.g., ΔCSA/ΔP), tension (e.g., P·r, where P and r arethe intraluminal pressure and radius of a cylindrical organ), stress(e.g., P·r/h where h is the wall thickness of the cylindrical organ),strain (e.g., (C−C_(d))/C_(d) where C is the inner circumference andC_(d) is the circumference in diastole) and wall shear stress (e.g., 4μQ/r³ where μ, Q and r are the fluid viscosity, flow rate and radius ofthe cylindrical organ for a fully developed flow). These quantities canbe used in assessing the mechanical characteristics of the system inhealth and disease.

Method

In one approach, luminal cross-sectional area is measured by introducinga catheter from an exteriorly accessible opening (e.g., mouth, nose oranus for GI applications; or e.g., mouth or nose for airwayapplications) into the hollow system or targeted luminal organ. Forcardiovascular applications, the catheter can be inserted into theorgans in various ways; e.g., similar to conventional angioplasty. Inone embodiment, an 18 gauge needle is inserted into the femoral arteryfollowed by an introducer. A guide wire is then inserted into theintroducer and advanced into the lumen of the femoral artery. A 4 or 5Fr conductance catheter is then inserted into the femoral artery viawire and the wire is subsequently retracted. The catheter tip containingthe conductance electrodes can then be advanced to the region ofinterest by use of x-ray (i.e., fluoroscopy). In another approach, thismethodology is used on small to medium size vessels (e.g., femoral,coronary, carotid, iliac arteries, etc.).

In one approach, a minimum of two injections (with differentconcentrations and/or conductivities of NaCl) are required to solve forthe two unknowns, CSA and G_(p). In another approach, three injectionswill yield three set of values for CSA and G_(p) (although notnecessarily linearly independent), while four injections would yield sixset of values. In one approach, at least two solutions (e.g., 0.5% and1.5% NaCl solutions) are injected in the targeted luminal organ orvessel. Our studies indicate that an infusion rate of approximately 1ml/s for a five second interval is sufficient to displace the bloodvolume and results in a local pressure increase of less than 10 mmHg inthe coronary artery. This pressure change depends on the injection ratewhich should be comparable to the organ flow rate.

In one preferred approach, involving the application of Equations [4]and [5], the vessel is under identical or very similar conditions duringthe two injections. Hence, variables, such as, for example, the infusionrate, bolus temperature, etc., are similar for the two injections.Typically, a short time interval is to be allowed (1-2 minute period)between the two injections to permit the vessel to return to homeostaticstate. This can be determined from the baseline conductance as shown inFIG. 4 or 5. The parallel conductance is preferably the same or verysimilar during the two injections. In one approach, dextran, albumin oranother large molecular weight molecule can be added to the NaClsolutions to maintain the colloid osmotic pressure of the solution toreduce or prevent fluid or ion exchange through the vessel wall.

In one approach, the NaCl solution is heated to body temperature priorto injection since the conductivity of current is temperature dependent.In another approach, the injected bolus is at room temperature, but atemperature correction is made since the conductivity is related totemperature in a linear fashion.

In one approach, a sheath is inserted either through the femoral orcarotid artery in the direction of flow. To access the lower anteriordescending (LAD) artery, the sheath is inserted through the ascendingaorta. For the carotid artery, where the diameter is typically on theorder of 5-5.5 mm, a catheter having a diameter of 1.9 mm can be used,as determined from finite element analysis, discussed further below. Forthe femoral and coronary arteries, where the diameter is typically inthe range from 3.5-4 mm, so a catheter of about 0.8 mm diameter would beappropriate. The catheter can be inserted into the femoral, carotid orLAD artery through a sheath appropriate for the particular treatment.Measurements for all three vessels can be made similarly.

Described here are the protocol and results for one exemplary approachthat is generally applicable to most arterial vessels. The conductancecatheter was inserted through the sheath for a particular vessel ofinterest. A baseline reading of voltage was continuously recorded. Twocontainers containing 0.5% and 1.5% NaCl were placed in temperature bathand maintained at 37°. A 5-10 ml injection of 1.5% NaCl was made over a5 second interval. The detection voltage was continuously recorded overa 10 second interval during the 5 second injection. Several minuteslater, a similar volume of 1.5% NaCl solution was injected at a similarrate. The data was again recorded. Matlab was used to analyze the dataincluding filtering with high pass and with low cut off frequency (1200Hz). The data was displayed using Matlab and the mean of the voltagesignal during the passage of each respective solution was recorded. Thecorresponding currents were also measured to yield the conductance(G=I/V). The conductivity of each solution was calibrated with sixdifferent tubes of known CSA at body temperature. A model using Equation[10] was fitted to the data to calculate conductivity C. The analysiswas carried out in SPSS using the non-linear regression fit. Given C andG for each of the two injections, an excel sheet file was formatted tocalculate the CSA and G_(p) as per Equations [4] and [5], respectively.These measurements were repeated several times to determine thereproducibility of the technique. The reproducibility of the data waswithin 5%. Ultrasound (US) was used to measure the diameter of thevessel simultaneous with our conductance measurements. The detectionelectrodes were visualized with US and the diameter measurements wasmade at the center of the detection electrodes. The maximum differencesbetween the conductance and US measurements were within 10%.

FIGS. 4A, 4B, 5A and 5B illustrate voltage measurements in the bloodstream in the left carotid artery. Here, the data acquisition had asampling frequency of 75 KHz, with two channels—the current injected andthe detected voltage, respectively. The current injected has a frequencyof 5 KH, so the voltage detected, modulated in amplitude by theimpedance changing through the bolus injection will have a spectrum inthe vicinity of 5 KHz.

With reference to FIG. 4A there is shown a signal processed with a highpass filter with low cut off frequency (1200 Hz). The top and bottomportions 200, 202 show the peak-to-peak envelope detected voltage whichis displayed in FIG. 4B (bottom). The initial 7 seconds correspond tothe baseline; i.e., electrodes in the blood stream. The next 7 secondscorrespond to an injection of hyper-osmotic NaCl solution (1.5% NaCl).It can be seen that the voltage is decreased implying increaseconductance (since the injected current is constant). Once the NaClsolution is washed out, the baseline is recovered as can be seen in thelast portion of the FIGS. 4A and 4B. FIGS. 5A and 5B show similar datacorresponding to 0.5% NaCl solutions.

The voltage signals are ideal since the difference between the baselineand the injected solution is apparent and systematic. Furthermore, thepulsation of vessel diameter can be seen in the 0.5% and 1.5% NaClinjections (FIGS. 4 and 5, respectively). This allows determination ofthe variation of CSA throughout the cardiac cycle as outline above.

The NaCl solution can be injected by hand or by using a mechanicalinjector to momentarily displace the entire volume of blood or bodilyfluid in the vessel segment of interest. The pressure generated by theinjection will not only displace the blood in the antegrade direction(in the direction of blood flow) but also in the retrograde direction(momentarily push the blood backwards). In other visceral organs whichmay be normally collapsed, the NaCl solution will not displace blood asin the vessels but will merely open the organs and create a flow of thefluid. In one approach, after injection of a first solution into thetreatment or measurement site, sensors monitor and confirm baseline ofconductance prior to injection of a second solution into the treatmentsite.

The injections described above are preferably repeated at least once toreduce errors associated with the administration of the injections, suchas, for example, where the injection does not completely displace theblood or where there is significant mixing with blood. It will beunderstood that any bifurcation(s) (with branching angle near 90degrees) near the targeted luminal organ can cause an overestimation ofthe calculated CSA. Hence, generally the catheter should be slightlyretracted or advanced and the measurement repeated. An additionalapplication with multiple detection electrodes or a pull back or pushforward during injection will accomplish the same goal. Here, an arrayof detection electrodes can be used to minimize or eliminate errors thatwould result from bifurcations or branching in the measurement ortreatment site.

In one approach, error due to the eccentric position of the electrode orother imaging device can be reduced by inflation of a balloon on thecatheter. The inflation of balloon during measurement will place theelectrodes or other imaging device in the center of the vessel away fromthe wall. In the case of impedance electrodes, the inflation of ballooncan be synchronized with the injection of bolus where the ballooninflation would immediately precede the bolus injection. Our results,however, show that the error due to catheter eccentricity is small.

The CSA predicted by Equation [4] corresponds to the area of the vesselor organ external to the catheter (i.e., CSA of vessel minus CSA ofcatheter). If the conductivity of the NaCl solutions is determined bycalibration from Equation [10] with various tubes of known CSA, then thecalibration accounts for the dimension of the catheter and thecalculated CSA corresponds to that of the total vessel lumen as desired.In one embodiment, the calibration of the CSA measurement system will beperformed at 37° C. by applying 100 mmHg in a solid polyphenolenoxideblock with holes of known CSA ranging from 7.065 mm² (3 mm in diameter)to 1017 mm² (36 in mm). If the conductivity of the solutions is obtainedfrom a conductivity meter independent of the catheter, however, then theCSA of the catheter is generally added to the CSA computed from Equation[4] to give the desired total CSA of the vessel.

The signals are generally non-stationary, nonlinear and stochastic. Todeal with non-stationary stochastic functions, one can use a number ofmethods, such as the Spectrogram, the Wavelet's analysis, theWigner-Ville distribution, the Evolutionary Spectrum, Modal analysis, orpreferably the intrinsic model function (IMF) method. The mean orpeak-to-peak values can be systematically determined by theaforementioned signal analysis and used in Equation [4] to compute theCSA.

Referring to the embodiment shown in FIG. 6, the angioplasty balloon 30is shown distended within the coronary artery 150 for the treatment ofstenosis. As described above with reference to FIG. 1B, a set ofexcitation electrodes 40, 41 and detection electrodes 42, 43 are locatedwithin the angioplasty balloon 30. In another embodiment, shown in FIG.7A, the angioplasty balloon 30 is used to distend the stent 160 withinblood vessel 150.

For valve area determination, it is not generally feasible to displacethe entire volume of the heart. Hence, the conductivity of blood ischanged by injection of hypertonic NaCl solution into the pulmonaryartery which will transiently change the conductivity of blood. If themeasured total conductance is plotted versus blood conductivity on agraph, the extrapolated conductance at zero conductivity corresponds tothe parallel conductance. In order to ensure that the two innerelectrodes are positioned in the plane of the valve annulus (2-3 mm), inone preferred embodiment, the two pressure sensors 36 are advantageouslyplaced immediately proximal and distal to the detection electrodes (1-2mm above and below, respectively) or several sets of detectionelectrodes (see, e.g., FIGS. 1D and 1F). The pressure readings will thenindicate the position of the detection electrode relative to the desiredsite of measurement (aortic valve: aortic-ventricular pressure; mitralvalve: left ventricular-atrial pressure; tricuspid valve: rightatrial-ventricular pressure; pulmonary valve: rightventricular-pulmonary pressure). The parallel conductance at the site ofannulus is generally expected to be small since the annulus consistsprimarily of collagen which has low electrical conductivity. In anotherapplication, a pull back or push forward through the heart chamber willshow different conductance due to the change in geometry and parallelconductance. This can be established for normal patients which can thenbe used to diagnose valvular stensosis.

In one approach, for the esophagus or the urethra, the procedures canconveniently be done by swallowing fluids of known conductances into theesophagus and infusion of fluids of known conductances into the urinarybladder followed by voiding the volume. In another approach, fluids canbe swallowed or urine voided followed by measurement of the fluidconductances from samples of the fluid. The latter method can be appliedto the ureter where a catheter can be advanced up into the ureter andfluids can either be injected from a proximal port on the probe (willalso be applicable in the intestines) or urine production can beincreased and samples taken distal in the ureter during passage of thebolus or from the urinary bladder.

In one approach, concomitant with measuring the cross-sectional area andor pressure gradient at the treatment or measurement site, a mechanicalstimulus is introduced by way of inflating the balloon or by releasing astent from the catheter, thereby facilitating flow through the stenosedpart of the organ. In another approach, concomitant with measuring thecross-sectional area and or pressure gradient at the treatment site, oneor more pharmaceutical substances for diagnosis or treatment of stenosisis injected into the treatment site. For example, in one approach, theinjected substance can be smooth muscle agonist or antagonist. In yetanother approach, concomitant with measuring the cross-sectional areaand or pressure gradient at the treatment site, an inflating fluid isreleased into the treatment site for release of any stenosis ormaterials causing stenosis in the organ or treatment site.

Again, it will be noted that the methods, systems, and cathetersdescribed herein can be applied to any body lumen or treatment site. Forexample, the methods, systems, and catheters described herein can beapplied to any one of the following exemplary bodily hollow systems: thecardiovascular system including the heart; the digestive system; therespiratory system; the reproductive system; and the urogential tract.

Finite Element Analysis:

In one preferred approach, finite element analysis (FEA) is used toverify the validity of Equations [4] and [5]. There are two majorconsiderations for the model definition: geometry and electricalproperties. The general Equation governing the electric scalar potentialdistribution, V, is given by Poisson's Equation as:

∇·(C∇V)=−I  [13]

where C, I and ∇ are the conductivity, the driving current density andthe del operator, respectively. Femlab or any standard finite elementpackages can be used to compute the nodal voltages using Equation [13].Once V has been determined, the electric field can be obtained from asE=−∇V.

The FEA allows the determination of the nature of the field and itsalteration in response to different electrode distances, distancesbetween driving electrodes, wall thicknesses and wall conductivities.The percentage of total current in the lumen of the vessel (% I) can beused as an index of both leakage and field homogeneity. Hence, thevarious geometric and electrical material properties can be varied toobtain the optimum design; i.e., minimize the non-homogeneity of thefield. Furthermore, we simulated the experimental procedure by injectionof the two solutions of NaCl to verify the accuracy of Equation [4].Finally, we assessed the effect of presence of electrodes and catheterin the lumen of vessel. The error terms representing the changes inmeasured conductance due to the attraction of the field to theelectrodes and the repulsion of the field from the resistive catheterbody were quantified.

We solved the Poisson's Equation for the potential field which takesinto account the magnitude of the applied current, the location of thecurrent driving and detection electrodes, and the conductivities andgeometrical shapes in the model including the vessel wall andsurrounding tissue. This analysis suggest that the following conditionsare optimal for the cylindrical model: (1) the placement of detectionelectrodes equidistant from the excitation electrodes; (2) the distancebetween the current driving electrodes should be much greater than thedistance between the voltage sensing electrodes; and (3) the distancebetween the detection and excitation electrodes is comparable to thevessel diameter or the diameter of the vessel is small relative to thedistance between the driving electrodes. If these conditions aresatisfied, the equipotential contours more closely resemble straightlines perpendicular to the axis of the catheter and the voltage dropmeasured at the wall will be nearly identical to that at the center.Since the curvature of the equipotential contours is inversely relatedto the homogeneity of the electric field, it is possible to optimize thedesign to minimize the curvature of the field lines. Consequently, inone preferred approach, one or more of conditions (1)-(3) describedabove are met to increase the accuracy of the cylindrical model.

Theoretically, it is impossible to ensure a completely homogeneous fieldgiven the current leakage through the vessel wall into the surroundingtissue. We found that the iso-potential line is not constant as we moveout radially along the vessel as stipulated by the cylindrical model. Inone embodiment, we consider a catheter with a radius of 0.55 mm whosedetected voltage is shown in FIGS. 7B and 7C for two different NaClsolutions (0.5% and 1.5%, respectively). The origin corresponds to thecenter of the catheter. The first vertical line 220 represents the innerpart of the electrode which is wrapped around the catheter and thesecond vertical line 221 is the outer part of the electrode in contactwith the solution (diameter of electrode is approximately 0.25 mm). Thesix different curves, top to bottom, correspond to six different vesselswith radii of 3.1, 2.7, 2.3, 1.9, 1.5 and 0.55 mm, respectively. It canbe seen that a “hill” occurs at the detection electrode 220, 221followed by a fairly uniform plateau in the vessel lumen followed by anexponential decay into the surrounding tissue. Since the potentialdifference is measured at the detection electrode 220, 221, oursimulation generates the “hill” whose value corresponds to theequivalent potential in the vessel as used in Equation [4]. Hence, foreach catheter size, we varied the dimension of the vessel such thatEquation [4] is exactly satisfied. Consequently, we obtained the optimumcatheter size for a given vessel diameter such that the distributivemodel satisfies the lumped Equations (Equation [4] and [5]). In thisway, we can generate a relationship between vessel diameter and catheterdiameter such that the error in the CSA measurement is less than 5%. Inone embodiment, different diameter catheters are prepackaged and labeledfor optimal use in certain size vessel. For example, for vesseldimension in the range of 4-5 mm, 5-7 mm or 7-10 mm, our analysis showsthat the optimum diameter catheters will be in the range of 0.91.4,1.4-2 or 2-4.6 mm, respectively. The clinician can select theappropriate diameter catheter based on the estimated vessel diameter ofinterest. This decision will be made prior to the procedure and willserve to minimize the error in the determination of lumen CSA.

The present disclosure also includes disclosure of impedance devices andsystems having particular electrode spacing, which is used to obtainoptimal conductance and/or fluid velocity measurements, as well asdevices and systems having a new and unique arrangements of electrodesto facilitate optimal conductance and fluid velocity measurements.

Various devices and systems of the present disclosure having atetrapolar arrangement of electrodes 25, 26, 27, 28, as shown in FIGS.1A, 1B, and 1E, for example, may have a particular spacing of electrodesso to facilitate optimal conductance measurements. As referenced above,and in at least one exemplary embodiment, electrodes 26 and 28 arespaced 1 mm apart and form the inner (detection) electrodes, andelectrodes 25 and 27 are spaced 4-5 mm from either side of the innerelectrodes and form the outer (excitation) electrodes. In at least onespecific example, the electrodes have a 4-1-4 spacing arrangement, whichis indicative of the spacing (in millimeters) between electrodes 25, 26,27, 28. For example, and as shown in FIG. 1E, the electrodes, startingfrom the most distal electrode, are in order of 27, 28, 26, and 25. Withthe 4-1-4 arrangement (most distal first), at least one exemplary deviceembodiment of the present disclosure has an electrode spacing of orabout 4 mm between electrodes 25 and 26, of or about 1 mm betweenelectrodes 26 and 28, and or of about 4 mm between electrodes 28 and 27.Such a spatial arrangement about a wire embodiment, as shown in FIG. 1Efor example, or a catheter embodiment, as shown in FIGS. 1A-1D forexample, may be optimal for obtaining conductance (and eventual sizing)measurements within relatively small luminal organs.

Such embodiments, as shown in FIGS. 1A-1E, are referred to tetrapolarembodiments as they each comprise four electrodes in a tetrapolararrangement (outside of a balloon 30) to facilitate sizing measurementswithin luminal organs. However, the addition of a fifth electrode,specifically and uniquely placed most proximal to the tetrapolarelectrodes, can allow for optimal fluid velocity measurements inaddition to sizing measurements as referenced herein. Embodiments ofdevices and systems of the present disclosure having a five-electrodearrangement, as provided in further detail below, are referred to hereinas “pentapolar” embodiments.

An exemplary device of the present disclosure having a pentapolararrangement of electrodes, and therefore capable of obtaining optimalsizing measurements as well as optimal fluid velocity measurements dueto their unique and particular arrangement and operation of electrodes,is shown in FIG. 8A. As shown in FIG. 8A, an exemplary device 300, whichmay have one or more features of various other devices and systems ofthe present disclosure, such as catheter 20 shown in FIG. 1A, catheter39 shown in FIG. 1B, catheter 21 shown in FIG. 1C, catheter 22 shown inFIG. 22, and wire 18 shown in FIG. 1E, for example, comprises anelongated body 302 with various electrodes positioned thereon ortherein. Body 302, in various embodiments, may comprise various wires orcatheters useful in the medical arts that are configured with anexemplary unique arrangement of electrodes as referenced herein.

As shown in FIG. 8A, an exemplary device 300 of the present comprisesfive electrodes, namely electrodes 304 (corresponding to electrode “A”),306 (corresponding to electrode “B”), 308 (corresponding to electrode“C”), 310 (corresponding to electrode “D”), and 312 (corresponding toelectrode “E”). Such electrodes, as shown in FIGS. 8A and 8B, may bereferred to as a detector 314, whereby detector 314 is operable toobtain sizing measurements as well as fluid velocity measurements. In atleast one embodiment, the electrodes of device 300 have a 4-1-4-8spacing arrangement, which is indicative of the spacing (in millimeters)between electrodes 304, 306, 308, 310, 312. For example, and as shown inFIG. 8A, the electrodes, starting from the most distal electrode, are inorder of 304, 306, 308, 310, and 312. With the 4-1-4-8 arrangement (mostdistal first), at least one exemplary device 300 embodiment of thepresent disclosure has an electrode spacing of or about 4 mm betweenelectrodes 304 and 306, of or about 1 mm between electrodes 306 and 308,of or about 4 mm between electrodes 308 and 310, and of or about 8 mmbetween electrodes 310 and 312. This spacing is in reference to at leastone embodiment of a device 300 of the present disclosure, noting thatsaid spacing is not arbitrary given the special considerations relatingto impedance, as an arbitrary electrode spacing would likely result in adevice that either can only obtain conductance measurements with a veryhigh error percentage, or result in a device that cannot effectivelyobtain a conductance measurement regardless of error.

With respect to electrode 312 in particular, it is noted that in theabove-referenced embodiment, electrode 312 is spaced furthest away fromits adjacent electrode, namely electrode 310, than any other electrodespacing upon device 300. Such spacing allows an exemplary device 300 ofthe present disclosure to not only obtain optimal sizing measurements,but optimal velocity measurements as well.

The device 300 embodiment shown in FIG. 8A, and the exemplary catheterand wire embodiments shown in FIGS. 1A-1E, for example, can be used toobtain sizing measurements in a similar fashion. For example, andregarding a device 300 embodiment having a pentapolar arrangement ofelectrodes, the four most distal electrodes can be used to obtain sizingmeasurements similar to a device having a tetrapolar arrangement ofelectrodes. For example, an exemplary device 300 embodiment, such asshown in FIG. 8A, can be used to obtain a sizing measurement within aluminal organ by way of exciting using electrodes A and D (namelyelectrodes 304 and 310) and detecting using electrodes B and C (namelyelectrodes 306 and 308), similar to the excitation of electrodes 25 and27 and the detection using electrodes 26 and 28 as generally referencedherein with respect to various device and system embodiments.

Such a tetrapolar arrangement could also be used to obtain fluidvelocity measurements, but there is a clear compromise with respect tospacing and accuracy of the sizing and velocity measurements when usinga tetrapolar arrangement of electrodes. For example, one would desire tohave the inner detection electrodes (namely electrodes 26 and 28 asshown in FIG. 1A, for example, or electrodes B and C (namely electrodes306 and 308) as shown in FIG. 8A) be relatively close together to obtainoptimal sizing measurements. However, and if using a tetrapolararrangement of electrodes to measure velocity, one would use electrodes27 and 28 together and would also use electrodes 25 and 26 together, sothat 27&28 and 25&26 act as the two detectors, separated by a distance,to obtain velocity measurements. However, when electrodes 26 and 28 arerelatively close together, the effective distance between the twovelocity detectors (namely 27&28 and 25&26) is very small, leading torelatively inaccurate or unreliable velocity measurements. If the innerelectrodes (electrodes 26 and 28) are spaced further apart so to obtaina more accurate and reliable velocity measurement, the accuracy andreliability of the sizing measurements decreases as the distance betweenthe inner electrodes (used as detectors for sizing) increases past 1 mm,for example.

To overcome this inherent compromise, the present disclosure providesfor various devices 300 having a pentapolar arrangement so that four ofthe five electrodes can be used to obtain optimal sizing measurements,and a different four of the five electrodes can be used to obtainoptimal fluid velocity measurements. For example, and using device 300as shown in FIG. 8A as an example, device 300 could be used to obtainsizing measurements by exciting electrodes A and D and detecting usingelectrodes B and C. Device 300 could also then be used to obtainvelocity measurements by exciting electrodes A and E and by detectingusing electrodes A&B and electrodes C&E.

The exemplary 4-1-4-8 configuration referenced herein is an exemplaryconfiguration optimized for sizing and fluid velocity measurementswithin mammalian luminal organs whereby sizing (such as sizing toidentify an appropriately-sized stent, for example) is relativelycommon. However, for larger luminal organs, a different configurationmay be required so that the electrode spacing is sufficient to obtain,for example, a luminal cross-sectional area measurement for a luminalorgan larger than a typical mammalian artery, for example. As referencedin at least one embodiment herein, the 4-1-4-8 arrangement correspond tospacings of 4 mm, 1 mm, 4 mm, and 8 mm, and in other embodiments, the4-1-4-8 arrangement may be indicative of a spacing ratio different thanthe corresponding millimeters.

Another exemplary embodiment of a device 300 of the present disclosureis shown in FIG. 8B. As shown in FIG. 8B, an exemplary device 300comprises a body 302 and a balloon 30 positioned thereon proximal todetector 314 so that any gas and/or fluid injected through body 302 intoballoon 30 by way of a suction/infusion port 35 will not leak into apatient's body when such a device 300 is positioned therein.

As shown in FIG. 8B, device 500 comprises a second detector 316, whereindetector 316, in at least one embodiment, comprises a tetrapolararrangement of two excitation electrodes 40, 41 and two detectionelectrodes 42, 43 located inside balloon 30 for accurate determinationof the balloon 30 cross-sectional area during sizing of a valve annulus.Such a tetrapolar arrangement of electrodes (excitation, detection,detection, and excitation, in that order) as shown in FIG. 8B wouldallow sizing within balloon 30, including the determination of balloon30 cross-sectional area at various stages of inflation.

As shown in FIG. 8B, device 300 may comprise a catheter (an exemplarybody 300), wherein balloon 30 is positioned thereon. In addition, anexemplary embodiment of a device 300, as shown in FIG. 8B, comprises apressure transducer 48 capable of measuring the pressure of a gas and/ora liquid present within balloon 30. Device 300, in at least oneembodiment as referenced herein, also has a suction/infusion port 35defined within catheter 39 inside balloon 30, whereby suction/infusionport 35 permits the injection of a gas and/or a fluid from a lumen ofcatheter 39 into balloon 30, and further permits the removal of a gasand/or a fluid from balloon 30 back into catheter 39.

The exemplary embodiments of devices 300 shown in FIGS. 8A and 8B arenot intended to be the sole embodiments of said devices 300, as variousdevices 300 of the present disclosure may comprise additional componentsas shown in various other figures and described herein. For example, anexemplary system of the present disclosure may comprise a device 300coupled to one more components shown in FIG. 3 just as catheter 20 showntherein is coupled thereto.

At least one embodiment of an exemplary device 300 of the presentdisclosure is shown in FIG. 9A. As shown in FIG. 9A, electrodes A, B, C,and D (numbered as electrodes 304, 306, 308, and 310 in the figure) areshown in a 4-1-4 tetrapolar arrangement. The numbers appearing belowdevice 300 in the FIG. 9A represent the spacing between electrodes inmillimeters and also identify an approximate 1 mm width of eachelectrode.

The distance between excitation electrodes would be at least two times(2×) the diameter of the vessel being sized. For example, in a 4-1-4tetrapolar arrangement of electrodes, and considering that eachexemplary electrode itself is approximately 1 mm in diameter, thedistance between the two excitation electrodes (electrodes 304 and 310)is 11 mm. This calculation is identified by way of the measurementsshown in FIG. 9A, whereby each electrode is shown as having a 1 mmlength, and whereby the electrodes are shown in a 4-1-4 tetrapolararrangement (namely 4 mm, 1 mm, and 4 mm from one another). With such anarrangement and size, vessels of up to about 5 mm in diameter (such ascoronary vessels) can be measured, as the distance between excitationelectrodes (11 mm) is at least two times the diameter (up to about 5 mm)being measured.

Peripheral vessels, having diameters as large as 10 mm in someinstances, would require a different electrode spacing than a 4-1-4arrangement, as such an arrangement would not obtain accuratemeasurements within a vessel of that size. For example, if a device 300having a 4-1-4 tetrapolar arrangement of electrodes were used to size avessel having a 10 mm diameter, the electric field would form a relativesphere instead of a relative cylindrical shape, resulting in aninaccurate impedance measurement.

Accordingly, an exemplary device 300 of the present disclosureconfigured to size peripheral vessels is shown in FIG. 9B. As shown inFIG. 9B, electrodes A, B, C, and D (numbered as electrodes 304, 306,308, and 310 in the figure) are shown in a 5-2-10 tetrapolararrangement. The numbers appearing below device 300 in the FIG. 9Brepresent the spacing between electrodes in millimeters and alsoidentify an approximate 1 mm width of each electrode. As shown in FIG.9B, device 300 has a 5-2-10 tetrapolar arrangement of electrodes,whereby the most distal electrode (electrode 304) is 5 mm from itsadjacent detection electrode (electrode 306), the two detectionelectrodes (electrodes 306 and 308) are 2 mm from one another, and themore proximal detection electrode (electrode 308) is 10 mm from theproximal excitation electrode (electrode 310). In such an arrangement,the distance between the two excitation electrodes 304, 310 is 19 mm,which is calculated by estimating the width of each electrode as 1 mmand adding the 5 mm, 2 mm, and 1 mm spacing to the two detectionelectrodes 306, 308. With such an arrangement and size, vessels of up toabout 9 mm or 10 mm in diameter can be precisely measured.

In general, the further apart the excitation electrodes are positionedfrom one another, the greater the overall parallel conductance, meaningthat more current is lost through the vessel itself. Because of thisloss, injected current has a fraction within the lumen and a fractionwithin the surrounding tissue. Given the separation of excitationelectrodes, and to get a proper signal to noise ratio, the detectionelectrodes are expanded from 1 mm to 2 mm in the 5-2-10 electrodearrangement.

Referring back to coronary vessel sizing (up to about 5 mm in diameter),and as referenced generally above, it is preferred to add a fifthelectrode to the tetrapolar arrangement to obtain velocity measurementsand effectively decouple sizing from velocity. However, and in attemptsto optimize a tetrapolar arrangement of electrodes useful for accuratesizing and velocity measurements, a 3-1-6 tetrapolar arrangement wasattempted (instead of 4-1-4), and such an arrangement was not successfulin obtaining accurate impedance measurements. However, when a 3-2-6arrangement was tried, it was successfully able to obtain sizing andvelocity measurements.

Another exemplary embodiment of an exemplary device 300 of the presentdisclosure is shown in FIG. 10A. As shown in FIG. 10A, electrodes A, B,C, and D (numbered as electrodes 304, 306, 308, and 310 in the figure)are shown in a 3-2-6 tetrapolar arrangement. The numbers appearing belowdevice 300 in the FIG. 10A also represent the spacing between electrodesin millimeters, and also identify an approximate 1 mm width of eachelectrode.

With a 3-2-6 arrangement, for example, velocity measurements may beobtained by measuring using the two distal electrodes (electrodes 304and 306, 3 mm apart) and the two proximal electrodes (electrodes 308 and310, 6 mm apart). When a constant voltage is applied to the vessel, avoltage drop would be indicative of a first deflection (the two proximalelectrodes) and a second deflection (the two distal electrodes) as abolus of fluid passes across the electrodes. As the first deflectionwould be identified when the bolus hits the most proximal electrode(namely electrode D) and the second deflection would be identified whenthe bolus passes the electrode just proximal to the most distalelectrode (namely electrode B), the bolus would pass 9 mm after passingelectrode D before passing electrode B, resulting in an accuratevelocity determination.

An exemplary device having a 4-1-4-8 pentapolar arrangement ofelectrodes, as referenced above, would allow a bolus to travel 15 mmbetween the two trigger velocity measurements. For example, velocitymeasurements could be obtained in a 4-1-4-8 arrangement by excitingelectrodes A and E and by detecting using electrodes A&B and electrodesC&E, as referenced above. The two triggers would be at electrode E andelectrode B, so that the bolus would pass 8 mm (the distance betweenelectrodes E and D) plus 1 mm (the size of electrode D) plus 4 mm (thedistance between electrodes D and C) plus 1 mm (the size of electrode C)plus 1 mm (the distance between electrodes C and B), for a total of 15mm. As such, the use of a fifth electrode (electrode E) for velocitymeasurements effectively decouples the sizing and velocity measurementsin a 4-1-4-8 embodiment, and if there is no fifth electrode, a 3-2-6tetrapolar arrangement of electrodes could be used.

Accordingly, and as referenced above, an exemplary device 300 of thepresent disclosure comprises an elongated body 302 and a detector 314positioned upon elongated body 302, wherein detector 302 comprises atleast five electrodes and configured to obtain one or more conductancemeasurements generated using a first arrangement of four of the at leastfive electrodes and further configured to obtain one or more fluidvelocity measurements using a second arrangement of four of the at leastfive electrodes when elongated body 302 is positioned within a fluidenvironment of a mammalian luminal organ, wherein the first arrangementis different from the second arrangement. Such an exemplary device maycomprise a wire and a catheter having the aforementioned features.

In at least one embodiment, at least three electrodes of the at leastfive electrodes are capable of excitation to generate an electric fieldwhen a current source capable of supplying electrical current to the atleast three electrodes is operably coupled thereto, and at least twoelectrodes of the at least five electrodes are capable of are capable ofobtaining one or more luminal organ measurements selected from the groupconsisting of the one or more conductance measurements and the one ormore fluid velocity measurements. In various embodiments, when the atleast two electrodes are operably connected to a data acquisition andprocessing system, the data acquisition and processing system is capableof receiving the one or more luminal organ measurements and calculatinga cross-sectional area of the luminal organ based in part upon the oneor more luminal organ measurements and a known distance between the atleast two electrodes.

With respect to an exemplary device 300 of the present disclosure havingfive electrodes and not more than five electrodes (which can occur asprovided in detail below), said electrodes comprise a most distalelectrode (electrode 304), an electrode immediately adjacent to the mostdistal electrode (electrode 306), a most proximal electrode (electrode312), an electrode immediately adjacent to the most proximal electrode(electrode 310), and a central electrode positioned between theelectrode immediately adjacent to the most distal electrode and theelectrode immediately adjacent to the most proximal electrode (electrode308). In at least one embodiment, the first arrangement of electrodescomprises the most distal electrode (electrode 304), the electrodeimmediately adjacent to the most distal electrode (electrode 306), thecentral electrode (electrode 308), and the electrode immediatelyadjacent to the most proximal electrode (electrode 310), whereinelectrode 304 and electrode 310 are capable of excitation to generate anelectric field, and wherein electrode 306 and electrode 308 areconfigured to obtain the one or more conductance measurements within theelectric field. In various embodiments, one or more cross-sectionalareas can be calculated based in part upon the one or more conductancemeasurements and a known distance between electrode 306 and electrode308.

In at least one embodiment of a device 300 of the present disclosure,when body 302 is positioned within a fluid environment of a mammalianluminal organ and wherein when the fluid environment includes anindicator, the most proximal electrode (electrode 312) is operable todetect the indicator, and detection of the indicator facilitatesactivation of the first arrangement of electrodes so that the firstarrangement of electrodes can obtain the one or more conductancemeasurements within the electric field.

In various embodiments, the second arrangement of electrodes comprisesthe most distal electrode (electrode 304), the electrode immediatelyadjacent to the most distal electrode (electrode 306), the centralelectrode (electrode 308), and the most proximal electrode (electrode312), wherein electrode 304 and electrode 312 are capable of excitationto generate an electric field, wherein electrode 304 and electrode 306comprise a first fluid velocity detection electrode pair, and whereinelectrode 308 and electrode 312 comprise a second fluid velocitydetection pair. In such an embodiment, for example, body 302 ispositioned within the fluid environment and wherein the fluidenvironment comprises an indicator, movement of the indicator past thefirst fluid velocity detection electrode pair (electrode 304, 306) andthe second fluid velocity detection electrode pair (electrodes 308, 312)allows the first fluid velocity detection electrode pair and the secondfluid velocity detection electrode pair to obtain the one or more fluidvelocity measurements. As referenced herein, the term “indicator” isintended to include a substance or property within a fluid that can bedetected by an electrode, such as a salt, a dye, a specific chemical,etc., and is not intended to be limited to any particular detectablesubstance or property.

Another exemplary embodiment of a device 300 of the present disclosureis shown in FIG. 10B. As shown in FIG. 10B, an octapolar arrangement ofelectrodes having a 3-2-6-2-6-2-3 spacing arrangement is shown, wherebydevice 300 is operable to simultaneously obtain three cross-sectionalarea measurements. In such an embodiment, device 300 could be used to,for example, obtain cross-sectional areas within a vessel proximal to astenosis, at a stenosis, and distal to a stenosis.

FIG. 10B shows electrodes 304, 306, 308, 310, and 312 (corresponding toelectrodes A, B, C, D, and E, respectively) and three additionalelectrodes 1100, 1102, and 1104 (corresponding to electrodes F, G, andH, respectively), whereby electrodes A-H are in alphabetical orderstarting from the distal end of device 300 (electrode A) and movingtoward the proximal end of device 300 (electrode H). The numbersappearing below device 300 in the FIG. 10B also represent the spacingbetween electrodes in millimeters, and also identify an approximate 1 mmwidth of each electrode.

In such an embodiment, a distal sizing measurement can be obtained byexciting electrodes A and D (13 mm apart) and detecting with electrodesB and C (2 mm apart), a central sizing measurement can be obtained byexciting electrodes C and F (16 mm apart) and detecting with electrodesD and E (2 mm apart), and a proximal sizing measurement can be obtainedby exciting electrodes E and H (13 mm apart) and detecting withelectrodes F and G (2 mm apart). If device 300 is then moved to adifferent position within the luminal organ, three additional sizingmeasurements can be obtained simultaneously.

Velocity measurements can also be made using a device 300 having a3-2-6-2-6-2-3 octapolar spacing arrangement as shown in FIG. 10B. Withsuch an electrode arrangement, for example, velocity measurements may beobtained by exciting with electrodes A and H and measuring usingelectrodes H and D (electrodes 1104 and 310), providing a 13 mm-15 mmdistance between the two deflections to provide an accurate velocitymeasurement. As referenced above, when a constant voltage is applied tothe vessel, a voltage drop would be indicative of a first deflection(the two proximal electrodes) and a second deflection (the two distalelectrodes) as a bolus of fluid passes across the electrodes. As thefirst deflection would be identified when the bolus hits the mostproximal electrode (namely electrode H) and the second deflection wouldbe identified when the bolus passes electrode D, resulting in anaccurate velocity determination given the spacing between electrodes Dand H.

In use, and as referenced above, exemplary devices 300 can be introducedinto a luminal organ, and using one or more fluid injections, devices300 can be used to obtain conductance measurements (useful to determinecross-sectional areas, for example), and also used to determine fluidvelocity using the electrode arrangements referenced above.

In such an octapolar electrode arrangement, such as shown in FIG. 10B,the eight electrodes comprise a most distal electrode (electrode 304),an electrode immediately adjacent to the most distal electrode(electrode 306), a most proximal electrode (electrode 1104), anelectrode immediately adjacent to the most proximal electrode (electrode1102), a central distal electrode (electrode 310), a central proximalelectrode (electrode 312), an electrode immediately adjacent to anddistal to the central distal electrode (electrode 308), and an electrodeimmediately adjacent to and proximal to the central proximal electrode(electrode 1100). In such an embodiment, the most distal electrode(electrode 304) and the central distal electrode (electrode 310) arecapable of excitation to generate a distal electric field, wherein theelectrode immediately adjacent to and distal to the central distalelectrode (electrode 308) and the electrode immediately adjacent to andproximal to the central proximal electrode (electrode 1100) are capableof excitation to generate a central electric field, wherein the centralproximal electrode (electrode 312) and the most proximal electrode(electrode 1104) are capable of excitation to generate a proximalelectric field, wherein the one or more conductance measurements can beobtained within each of the distal electric field, the central electricfield, and the proximal electric field, and wherein one or morecross-sectional areas can be calculated based in part upon the one ormore conductance measurements and known distances between the electrodesused to generate the distal electric field, the central electric field,and the proximal electric field.

In various octapolar device 300 embodiments, the second arrangement ofelectrodes comprises the most distal electrode, the central distalelectrode, the central proximal electrode, and the most proximalelectrode, wherein the most distal electrode and the central distalelectrode comprise a first fluid velocity detection electrode pair, andwherein the central proximal electrode and the most proximal electrodecomprise a second fluid velocity detection pair. In at least oneembodiment, when the elongated body is positioned within the fluidenvironment and wherein the fluid environment comprises an indicator,movement of the indicator past the first fluid velocity detectionelectrode pair and the second fluid velocity detection electrode pairallows the first fluid velocity detection electrode pair and the secondfluid velocity detection electrode pair to obtain the one or more fluidvelocity measurements.

Again, it is noted that the various devices, systems, and methodsdescribed herein can be applied to any body lumen or treatment site. Forexample, the devices, systems, and methods described herein can beapplied to any one of the following exemplary bodily hollow organs: thecardiovascular system including the heart, the digestive system, therespiratory system, the reproductive system, and the urogenital tract.

While various embodiments of impedance devices for obtaining conductancemeasurements within luminal organs have been described in considerabledetail herein, the embodiments are merely offered by way of non-limitingexamples of the disclosure described herein. It will therefore beunderstood that various changes and modifications may be made, andequivalents may be substituted for elements thereof, without departingfrom the scope of the disclosure. Indeed, this disclosure is notintended to be exhaustive or to limit the scope of the disclosure.

Further, in describing representative embodiments, the disclosure mayhave presented a method and/or process as a particular sequence ofsteps. However, to the extent that the method or process does not relyon the particular order of steps set forth herein, the method or processshould not be limited to the particular sequence of steps described.Other sequences of steps may be possible. Therefore, the particularorder of the steps disclosed herein should not be construed aslimitations of the present disclosure. In addition, disclosure directedto a method and/or process should not be limited to the performance oftheir steps in the order written. Such sequences may be varied and stillremain within the scope of the present disclosure.

1. An impedance device, comprising: an elongated body; and a detectorpositioned upon the elongated body, the detector comprising at leastfour electrodes configured to obtain one or more conductancemeasurements within a luminal organ of at least 4 mm in diameter, the atleast four electrodes comprising at least a most distal electrode, anelectrode immediately adjacent to the most distal electrode, a proximalelectrode, and an electrode immediately adjacent to the proximalelectrode; wherein the most distal electrode is spaced at least 3 mmfrom the an electrode immediately adjacent to the most distal electrode,wherein the electrode immediately adjacent to the most distal electrodeis spaced at least 2 mm from the electrode immediately adjacent to theproximal electrode, and wherein the electrode immediately adjacent tothe proximal electrode is spaced at least 6 mm from the proximalelectrode.
 2. The impedance device of claim 1, wherein the most distalelectrode is spaced at least 5 mm from the an electrode immediatelyadjacent to the most distal electrode, and wherein the electrodeimmediately adjacent to the proximal electrode is spaced at least 10 mmfrom the proximal electrode.
 3. The impedance device of claim 1, whereinthe elongated body is selected from the group consisting of a wire and acatheter.
 4. The impedance device of claim 1, wherein the most distalelectrode and the proximal electrode are spaced at or about 11 mm fromeach other.
 5. The impedance device of claim 1, wherein the most distalelectrode and the proximal electrode are spaced at or about 18 mm fromeach other.
 6. The impedance device of claim 1, further comprising: aninflatable balloon positioned along the longitudinal axis of theelongated body located proximal to the detector, wherein the inflatableballoon is in communication with a lumen defined within the elongatedbody.
 7. The impedance device of claim 6, further comprising: atetrapolar detector positioned upon the elongated body within theballoon, the tetrapolar detector comprising two excitation electrodesand two detection electrodes operable to obtain one or more ballooncross-sectional areas.
 8. An impedance device, comprising: an elongatedbody; and a detector positioned upon the elongated body, the detectorcomprising at least four electrodes configured to obtain one or moreconductance measurements within a luminal organ of at least 4 mm indiameter, the at least four electrodes comprising at least a most distalelectrode, an electrode immediately adjacent to the most distalelectrode, a proximal electrode, and an electrode immediately adjacentto the proximal electrode; wherein the electrode immediately adjacent tothe most distal electrode is spaced greater than 1 mm from the electrodeimmediately adjacent to the proximal electrode.
 9. The impedance deviceof claim 8, wherein the most distal electrode is spaced at least 3 mmfrom the an electrode immediately adjacent to the most distal electrode,wherein the electrode immediately adjacent to the most distal electrodeis spaced at least 2 mm from the electrode immediately adjacent to theproximal electrode and wherein the electrode immediately adjacent to theproximal electrode is spaced at least 6 mm from the proximal electrode.10. The impedance device of claim 8, wherein the most distal electrodeis spaced at least 5 mm from the an electrode immediately adjacent tothe most distal electrode, wherein the electrode immediately adjacent tothe most distal electrode is spaced at least 2 mm from the electrodeimmediately adjacent to the proximal electrode and wherein the electrodeimmediately adjacent to the proximal electrode is spaced at least 10 mmfrom the proximal electrode.
 11. The impedance device of claim 8,further comprising: four additional electrodes positioned upon theelongated body, the four additional electrodes and the at least fourelectrodes comprising at least eight electrodes, wherein two electrodesof the at least eight electrodes are configured to excite an electricfield within a luminal organ, and wherein six electrodes of the at leasteight electrodes form three pairs of detection electrodes that areconfigured to sense the electric field at three locations along theelongated body.
 12. The impedance device of claim 8, further comprising:ten additional electrodes positioned upon the elongated body, the tenadditional electrodes and the at least four electrodes comprising atleast fourteen electrodes, wherein two electrodes of the at leastfourteen electrodes are configured to excite an electric field within aluminal organ, and wherein twelve electrodes of the at least fourteenelectrodes form six pairs of detection electrodes that are configured tosense the electric field at six locations along the elongated body. 13.An impedance device, comprising: an elongated body; and a detectorpositioned upon the elongated body, the detector comprising at leastfive electrodes, the at least five electrodes comprising: a most distalelectrode, an electrode immediately adjacent to the most distalelectrode, a most proximal electrode, an electrode immediately adjacentto the most proximal electrode, and a central electrode positionedbetween the electrode immediately adjacent to the most distal electrodeand the electrode immediately adjacent to the most proximal electrode,wherein the electrode immediately adjacent to the most distal electrodeis spaced at least 1 mm from the central electrode; wherein theimpedance device is configured to obtain one or more conductancemeasurements and one of more fluid velocity measurements when theelongated body is positioned within a fluid environment of a mammalianluminal organ.
 14. The impedance device of claim 13, wherein theelongated body is selected from the group consisting of a wire and acatheter.
 15. The impedance device of claim 13, wherein a firstarrangement of electrodes comprises the most distal electrode, theelectrode immediately adjacent to the most distal electrode, the centralelectrode, and the electrode immediately adjacent to the most proximalelectrode, wherein the most distal electrode and the electrodeimmediately adjacent to the most proximal electrode are capable ofexcitation to generate an electric field, and wherein the electrodeimmediately adjacent to the most distal electrode and the centralelectrode are configured to obtain the one or more conductancemeasurements within the electric field.
 16. The impedance device ofclaim 15, wherein one or more cross-sectional areas can be calculatedbased in part upon the one or more conductance measurements and a knowndistance between the electrode immediately adjacent to the most distalelectrode and the central electrode.
 17. The impedance device of claim13, wherein the second arrangement of electrodes comprises the mostdistal electrode, the electrode immediately adjacent to the most distalelectrode, the central electrode, and the most proximal electrode,wherein the most distal electrode and the most proximal electrode arecapable of excitation to generate an electric field, wherein the mostdistal electrode and the electrode immediately adjacent to the mostdistal electrode comprise a first fluid velocity detection electrodepair, and wherein the central electrode and the most proximal electrodecomprise a second fluid velocity detection pair.
 18. The impedancedevice of claim 13, wherein the most distal electrode is spaced 4 mmfrom the an electrode immediately adjacent to the most distal electrode,wherein the electrode immediately adjacent to the most distal electrodeis spaced 1 mm from the central electrode, wherein the central electrodeis spaced 4 mm from the electrode immediately adjacent to the mostproximal electrode, and wherein the electrode immediately adjacent tothe most proximal electrode is spaced 8 mm from the most proximalelectrode.
 19. The impedance device of claim 13, wherein the most distalelectrode is spaced 3 mm from the an electrode immediately adjacent tothe most distal electrode, wherein the electrode immediately adjacent tothe most distal electrode is spaced 2 mm from the central electrode, andwherein the central electrode is spaced 6 mm from the electrodeimmediately adjacent to the most proximal electrode.
 20. The impedancedevice of claim 13, wherein the most distal electrode is spaced 5 mmfrom the an electrode immediately adjacent to the most distal electrode,wherein the electrode immediately adjacent to the most distal electrodeis spaced 2 mm from the central electrode, and wherein the centralelectrode is spaced 10 mm from the electrode immediately adjacent to themost proximal electrode.